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Selvaraj P Chandra G Jawahar MS Rani MV Rajeshwari DN Narayanan PR 《Journal of clinical immunology》2004,24(5):523-532
The regulatory role of vitamin D receptor (VDR) gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on vitamin D(3)-modulated macrophage phagocytosis with live Mycobacterium tuberculosis and lymphoproliferative response to M. tuberculosis culture filtrate antigen (CFA) was studied in patients with pulmonary tuberculosis (n = 46) and in normal healthy subjects (NHS) (n = 64). Vitamin D(3) at a concentration of 1 x 10(-7) M enhanced the phagocytic potential of normal subjects who had a phagocytic index of less than 20%. This increase was seen in subjects with the genotypes BB (p = 0.017), AA (p = 0.016), tt (p = 0.034), and FF (p = 0.013) and the extended genotype BBAAtt (p = 0.034). Normal subjects with BBAAtt performed better phagocytosis than individuals with bbaaTT genotype (p = 0.034). Vitamin D(3) at 10(-9), 10(-8), and 10(-7) M concentrations suppressed the lymphoproliferative response to CFA antigen in normal subjects. This decreased lymphocyte response was observed in normal individuals with the genotypes BB (p = 0.0009), tt (p = 0.016), and FF (p = 0.008) and the extended genotype BBAAtt (p = 0.02). Addition of vitamin D(3) had no significant effect on macrophage phagocytosis and lymphoproliferative response to CFA in pulmonary TB patients. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) or the downregulated VDR expression by virtue of the disease, which renders them inactive. The genotypes BB, tt, and the extended genotype BBAAtt may be associated with increased expression of VDR which in turn regulate the action of vitamin D(3) and modulate the immune functions to M. tuberculosis in NHS. 相似文献
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M. Karthik Selvaraj Tapan Kumar Das Nikhil Joseph Martin M. Shyam Sundar David V. Rajan 《Indian Journal of Orthopaedics》2021,55(3):723
IntroductionLatarjet procedure is commonly performed for recurrent anterior shoulder instability with glenoid side bone loss. Classic Latarjet procedure can be performed using specially designed drill guides, jigs, or by freehand technique. Here we have described a technical note on classic Latarjet procedure performed with freehand technique utilizing simple rulers and caliper. The functional and radiological outcomes of our patients have also been analysed.Material and Methods149 open classic Latarjet procedures were performed using our technique between March 2015 and July 2018. The mean age of the patients was 32.95 years (Range 22–59 years). The functional outcome of the patients was measured using Western Ontario Shoulder Instability (WOSI) and Oxford Shoulder Instability Score (OSIS) at 2 years of follow-up. Screw and graft positioning were studied in 24 consecutive patients with a postoperative computed tomography (CT) scan.ResultsThere was no incidence of recurrent subluxation or dislocation post-surgery. Mean OSIS score increased from 15.63 ± 3.20 preoperatively to 42.44 ± 3.88 postoperatively (p value < 0.05). WOSI score decreased significantly from 62.54% ± 8.24 to 10.26 ± 6.33 postoperatively at 2-year follow-up (p value < 0.05). Postoperative CT scan also showed satisfactory screw placement in all patients.ConclusionOpen Latarjet procedure performed using freehand technique provides good functional and radiological outcomes in patients with recurrent anterior shoulder instability with glenoid side bone loss.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00385-7. 相似文献
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Mohane Selvaraj Coumar Fang-Ying Tsai Jagat Rakesh Kanwar Sailu Sarvagalla Chun Hei Antonio Cheung 《Cancer treatment reviews》2013
Since the discovery of survivin (BIRC5) as a cancer-related molecule by Grazia Ambrosini and Dario C. Altieri at 1997, our knowledge related to the function of this molecule has been extended from simple apoptosis inhibition to complicated, interlinked processes that involve interference of mitosis, apoptosis, autophagy, and even DNA repair recently. However, despite the growing amount of knowledge related to survivin in the last ten years, the development of survivin inhibitors or survivin-related molecular therapies is surprisingly and relatively slow as compared to other therapeutic inhibitors for cancer treatment. Here, the molecular functions of survivin and the progress of development of survivin-targeting therapies are discussed in detail. Functional differences between different survivin-specific inhibitors are discussed from both structural and biochemical point of views. This review also reveals different challenges that scientists are currently facing in the development of survivin inhibitors for clinical application. Finally, future directions for the development of survivin-targeted therapies are discussed in this review. 相似文献
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Platelet activation leads to the incorporation of 32[PO4(2-)] into bovine coagulation factor Va and recombinant human factor VIII. In the presence of the soluble fraction from thrombin-activated platelets and (gamma-32P) adenosine triphosphate, radioactivity is incorporated exclusively into the M(r) = 94,000 heavy chain (H94) of factor Va and into the M(r) = 210,000 to 90,000 heavy chains as well into the M(r) = 80,000 light chain of factor VIII. Proteolysis of the purified phosphorylated M(r) = 94,000 factor Va heavy chain by activated protein C (APC) gave products of M(r) = 70,000, 24,000, and 20,000. Only the intermediate M(r) = 24,000 fragment contained radioactivity. Because the difference between the M(r) = 24,000 and M(r) = 20,000 fragments is located on the COOH-terminal end of the bovine heavy chain, phosphorylation of H94 must occur within the M(r) = 4,000 peptide derived from the carboxyl-terminal end of H94 (residues 663 through 713). Exposure of the radioactive factor VIII molecule to thrombin ultimately resulted in a nonradioactive light chain and an M(r) = 24,000 radioactive fragment that corresponds to the carboxyl-terminal segment of the A1 domain of factor VIII. Based on the known sequence of human factor VIII, phosphorylation of factor VIII by the platelet kinase probably occurs within the acidic regions 337 through 372 and 1649 through 1689 of the procofactor. These acidic regions are highly homologous to sequences known to be phosphorylated by casein kinase II. Results obtained using purified casein kinase II gave a maximum observed stoichiometry of 0.6 mol of 32[PO4(2-)]/mol of factor Va heavy chain and 0.35 mol of 32[PO4(2-)]/mol of factor VIII. Phosphoamino acid analysis of phosphorylated factor Va by casein kinase II or by the platelet kinase showed only the presence of phosphoserine while phosphoamino acid analysis of phosphorylated factor VIII by casein kinase II showed the presence of phosphothreonine as well as small amounts of phosphoserine. The platelet kinase responsible for the phosphorylation of the two cofactors was found to be inhibited by several synthetic protein kinase inhibitors. Finally, partially phosphorylated factor Va was found to be more sensitive to APC inactivation than its native counterpart. Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II- like kinase may downregulate the activity of the two cofactors. 相似文献